ACE inhibitors &amp;ndash; angiotensin II receptor antagonists: A useful combination therapy for ischemic heart disease

Saleem, TS Mohamed

doi:10.2147/oaem.s10507

Cited by 13 publications

(6 citation statements)

References 69 publications

(68 reference statements)

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“…This may be due to its nonselective action on both angiotensin II receptors type 1 (AT1) and type 2 (AT2). 43,44 AT2 is known to have opposing actions to AT1 and is expressed in human microvascular brain endothelial cells, yet its role in the BBB remains undefined. We hypothesize that ACEI inhibits angiotensin II production and minimizes the protective effect of AT1 inhibition by simultaneously blocking AT2 action.…”

Section: Discussionmentioning

confidence: 99%

“…However, in this study, we did not observe a protective association of ACEIs with epilepsy compared with other antihypertensive medications. This may be due to its nonselective action on both angiotensin II receptors type 1 (AT1) and type 2 (AT2) . AT2 is known to have opposing actions to AT1 and is expressed in human microvascular brain endothelial cells, yet its role in the BBB remains undefined.…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

Wen,

Otoo,

Tang

et al. 2024

JAMA Neurol

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ImportanceAnimal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking.ObjectiveTo evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension.Design, Setting, and ParticipantsThis retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), β-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024.ExposuresPropensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, β-blockers, CCBs, or a combination of these antihypertensive medications.Main Outcomes and MeasuresCox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups.ResultsOf 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received β-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, &gt;65 years), and β-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs β-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), β-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease.Conclusions and RelevanceThis cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

Wen,

Otoo,

Tang

et al. 2024

JAMA Neurol

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“…The worst-case scenario would occur if ANG II production and/or AT1R activity are reduced for any reason, e.g. using ACE inhibitors ( 30 ) ( Figure 1C ). In this case, ADAM-17 would not be consistently activated, leading to two concomitant situations: a) there would be more tACE2 available to facilitate the entry of the virus into host cells, and b) less biologically active sACE2 might result in more circulating free virus, with the potential to enter host cells via tACE2.…”

Section: Discussionmentioning

confidence: 99%

“…Reduction or equal levels of ANG II. Origin: Decrease in ANG II levels promoted by drugs, such as ACE inhibitors ( 30 ).…”

Section: Putative Changes In the Raas Related To Covid-19mentioning

confidence: 99%

Does Angiotensin II Peak in Response to SARS-CoV-2?

et al. 2021

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Human infection by the SARS-CoV-2 is causing the current COVID-19 pandemic. With the growing numbers of cases and deaths, there is an urgent need to explore pathophysiological hypotheses in an attempt to better understand the factors determining the course of the disease. Here, we hypothesize that COVID-19 severity and its symptoms could be related to transmembrane and soluble Angiotensin-converting enzyme 2 (tACE2 and sACE2); Angiotensin II (ANG II); Angiotensin 1-7 (ANG 1-7) and angiotensin receptor 1 (AT1R) activation levels. Additionally, we hypothesize that an early peak in ANG II and ADAM-17 might represent a physiological attempt to reduce viral infection via tACE2. This viewpoint presents: (1) a brief introduction regarding the renin-angiotensin-aldosterone system (RAAS), detailing its receptors, molecular synthesis, and degradation routes; (2) a description of the proposed early changes in the RAAS in response to SARS-CoV-2 infection, including biological scenarios for the best and worst prognoses; and (3) the physiological pathways and reasoning for changes in the RAAS following SARS-CoV-2 infection.

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“…Following an initial period of 5 min of stabilization, the flow is stopped for 9 minutes (ischemia) followed by reperfusion with K-H buffer for 12 minutes (reperfusion) [ 14 – 17 ].…”

Section: Methodsmentioning

confidence: 99%

Protective Role of Ramipril and Candesartan against Myocardial Ischemic Reperfusion Injury: A Biochemical and Transmission Electron Microscopical Study

Uduman¹,

Reddy²,

Punuru³

et al. 2016

Advances in Pharmacological Sciences

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The present study was designed to investigate the role of combined administration of Ramipril and Candesartan against in vitro myocardial ischemic reperfusion injury in rat. Male Wistar albino rats were divided into five groups (n = 6) and treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of global ischemia (5 min of stabilization, 9 min of global ischemia, and 12 min of reflow). Combination of Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of superoxide dismutase, reduced glutathione, catalase, and nitric oxide and decreased the levels of thiobarbituric acid reactive substances. In addition, the superior protective role of combination of Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well preserved myocardial tissue architecture in light microscopy and transmission electron microscopy analysis studies. The combination was proved to be effective in salvaging the myocardial tissue against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels are needed.

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ACE inhibitors – angiotensin II receptor antagonists: A useful combination therapy for ischemic heart disease

Cited by 13 publications

References 69 publications

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

Does Angiotensin II Peak in Response to SARS-CoV-2?

Protective Role of Ramipril and Candesartan against Myocardial Ischemic Reperfusion Injury: A Biochemical and Transmission Electron Microscopical Study

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